Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I.

By David J. Katzmann, M. Babst, S. Emr. Cell, 2001

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The multivesicular body (MVB) pathway is responsible for both the biosynthetic delivery of lysosomal hydrolases and the downregulation of numerous activated cell surface receptors which are degraded in the lysosome. We demonstrate that ubiquitination serves as a signal for sorting into the MVB pathway. In addition, we characterize a 350 kDa complex, ESCRT-I (composed of Vps23, Vps28, and Vps37), that recognizes ubiquitinated MVB cargo and whose function is required for sorting into MVB vesicles. This recognition event depends on a conserved UBC-like domain in Vps23. We propose that ESCRT-I represents a conserved component of the endosomal sorting machinery that functions in both yeast and mammalian cells to couple ubiquitin modification to protein sorting and receptor downregulation in the MVB pathway.

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/f0e4852fc8471baef8427bc80e5ce67b8c025623

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Citations in the corpus

Biogenesis and function of multivesicular bodies. (2007, background): “If such a supercomplex exists in vivo, it likely forms on membranes because biochemical analysis of soluble fractions finds ESCRTI and ESCRT-II as discrete complexes (Babst et al. 2002b, Katzmann et al. 2001).”
Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. (2001, background): “Approxiaddition to PPXY) can mark proteins for ubiquitination mately 4.2 million bait/prey pairs were tested, and prey encoding and entry into the Vps pathway and that other recogni- Tsg101 residues 7–390 were isolated twice (Tsg101 NCBI accession # NM_006292).tion motifs (in addition to PTAP) can t”
The ESCRT pathway. (2011, background): “Vps27/Hrsbindsclathrin heavychain via its clathrin box motif (Raiborg et al., 2001).”
Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake (2016, neutral): “In short, ESCRT I binds the ubiquitinated cargo on the endosomes, upon which ESCRT II is activated (Katzmann et al. 2001).”
Exosomes: endosomal-derived vesicles shipping extracellular messages. (2004, background): “Tsg101 is one of the components of the so-called endosomal sorting complex required for transport (ESCRT)-I [23].”
Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation (2003, background): “Monoubiquitination, by contrast, is involved in endocytic trafficking, both at the stage of receptor internalization at the plasma membrane and in the endosomal compartment where ubiquitinated receptors are sorted to a lysosomal compartment, thereby preventing their recycling to the plasma membran”
PPPYEPTAP Motif Is the Late Domain of Human T-Cell Leukemia Virus Type 1 Gag and Mediates Its Functional Interaction with Cellular Proteins Nedd4 and Tsg101 (2003, background): “Tsg101 is a protein known to function in vacuolar protein sorting machinery (2) by binding to monoubiquitinated proteins, thus driving their entry into the multivesicular body sorting machinery (24).”
Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “Vps34p is also important for the membrane invaginations in multivesicular bodies (MVB) (70, 71, 765) and for various forms of autophagy (779).”